PROJECT SUMMARY The genetic inheritance of specific risk alleles is widely accepted as a major contributing factor to many, if not all, mental illnesses. Moreover, recent studies found that the precise epigenetic regulation of gene expression is critical for normal learning and memory processes and is often disrupted in the diseased brain. However, despite recent concerted efforts of numerous neuroscientists and physicians, the links between precise molecular and synaptic defects resulting from (epi)genetic variation and specific brain circuit abnormalities that result in particular behavioral disorders remain rather poorly understood. Given the ongoing avalanche of new genetic/genomic data associated with neuropsychiatric disorders, there is a rapidly expanding need to train the next generation of neuroscientists to be facile in both modern molecular genetic approaches in different model systems, as well as in cutting edge molecular bioinformatics techniques that are required to link individual genes to normal brain functions and disease processes. The over-arching goal of this multi-disciplinary postdoctoral Training Program in Functional Neurogenomics is to support a training pipeline that fosters the development of new investigators with these skills. This competing renewal application will demonstrate an advancement and evolution in both the available training mentors and in cutting edge inter-disciplinary technical capabilities that builds on the substantial prior successes of this long-running program. Our efforts are supported by significant ongoing investments by Vanderbilt in new neuroscience leadership, faculty, educational programs, technological expertise and core facilities. Taken together, this provides a robust and rigorous environment for trainees to gain expertise in opportunities afforded by genetic model systems, the translation of human genetic findings into construct-valid animal models, in vivo manipulations of molecules, cells and circuits using advanced approaches, and in capturing the epigenetic, physiological, and behavioral consequences of such manipulations. The Program Director is Roger J. Colbran, Ph.D., Professor and Interim Chair of the Department of Molecular Physiology & Biophysics. Dr. Colbran has a long-standing, well-funded program investigating molecular mechanisms involved in synaptic plasticity using multi-disciplinary approaches from biochemical structure-function to mouse genetics and behavior. The Co-Director, J. David Sweatt, Ph.D., was recently recruited to Vanderbilt as the Chair of the Department of Pharmacology and has previously served on both the NIMH Advisory Council and the NIMH intramural program Board of Scientific Councilors. Dr. Sweatt has made numerous highly-cited contributions to understanding mechanisms underlying learning and memory in previous positions at Baylor College of Medicine and UAB, with a particular recent focus on the role of epigenetics in cognition and neural plasticity. The program leadership has a long-standing commitment to mentoring the next generation of neuroscientists, with a strong track record of facilitating the establishment of enduring and productive research careers for their trainees.